Respiratory and metabolic acidosis correction with the ADVanced Organ Support system

Aritz Perez Ruiz De Garibay,Johannes Honigschnabel,Bernhard Kreymann,John A Kellum

doi:10.1186/s40635-019-0269-7

Abstract

BackgroundThe lung, the kidney, and the liver are major regulators of acid-base balance. Acidosis due to the dysfunction of one or more organs can increase mortality, especially in critically ill patients. Supporting compensation by increasing ventilation or infusing bicarbonate is often ineffective. Therefore, direct removal of acid may represent a novel therapeutic approach. This can be achieved with the ADVanced Organ Support (ADVOS) system, an enhanced renal support therapy based on albumin dialysis. Here, we demonstrate proof of concept for this technology.MethodsAn ex vivo model of either hypercapnic (i.e., continuous CO2 supply) or lactic acidosis (i.e., lactic acid infusion) using porcine blood was subjected to hemodialysis with ADVOS. A variety of operational parameters including blood and dialysate flows, different dialysate pH settings, and acid and base concentrate compositions were tested. Comparisons with standard continuous veno-venous hemofiltration (CVVH) using high bicarbonate substitution fluid and continuous veno-venous hemodialysis (CVVHD) were also performed.ResultsSixty-one milliliters per minute (2.7 mmol/min) of CO2 was removed using a blood flow of 400 ml/min and a dialysate pH of 10 without altering blood pCO2 and HCO3− (36 mmHg and 20 mmol/l, respectively). Up to 142 ml/min (6.3 mmol/min) of CO2 was eliminated if elevated pCO2 (117 mmHg) and HCO3− (63 mmol/l) were allowed. During continuous lactic acid infusion, an acid load of up to 3 mmol/min was compensated. When acidosis was triggered, ADVOS multi normalized pH and bicarbonate levels within 1 h, while neither CVVH nor CVVHD could. The major determinants to correct blood pH were blood flow, dialysate composition, and initial acid-base status.ConclusionsIn conclusion, ADVOS was able to remove more than 50% of the amount of CO2 typically produced by an adult human. Blood pH was maintained stable within the physiological range through compensation of a metabolic acid load by albumin dialysate. These in vitro results will require confirmation in patients.

Highlights

Lung, kidney, and hepatic dysfunction are common in the critically ill, and acid-base regulation is frequently compromised in these patients
A dialysate flow of 800 ml/min was used throughout the study, which refers to the amount of fluid per minute being recirculated and detoxified in the ADVanced Organ Support (ADVOS) multi circuit by means of pH adjustments and filtration, instead of being discarded after a single pass
Influence of ADVOS multi operational settings on Carbon dioxide (CO2) removal In this experimental design, where blood was titrated with CO2 to maintain a blood pH between 7.35 and 7.45, CO2 removal with ADVOS multi depended on three variables: (1) the amount of CO2 being supplied, (2) the blood flow, and (3) the dialysate composition (Fig. 2 and Additional file 1: Table S1)

Summary

Introduction

Kidney, and hepatic dysfunction are common in the critically ill, and acid-base regulation is frequently compromised in these patients. Acidosis can impair several immune response mechanisms, including lymphocyte cytotoxicity, complement activation, or antibody binding to leukocytes [8]. Since some of these findings have been already reported in patients [7], acid-base imbalances should be considered in the context of a host response to an aggression, and not as an isolated insult. Acidosis due to the dysfunction of one or more organs can increase mortality, especially in critically ill patients. Direct removal of acid may represent a novel therapeutic approach This can be achieved with the ADVanced Organ Support (ADVOS) system, an enhanced renal support therapy based on albumin dialysis.

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Conclusion